Advances in proteomics research related to semaglutide: evidence from humans and animals

This review of 16 studies finds that semaglutide is associated with reproducible proteomic changes across multiple tissues and disease backgrounds, with recurring signals in fatty acid metabolism, mitochondrial function, inflammation, and extracellular matrix pathways. The evidence base is still limited by small samples, heterogeneous designs, and few human studies.

Narrative review — Review of human and animal studies. Population: Humans, animals, and in vitro models in semaglutide intervention studies. Sample size: 16 studies. Interventions: semaglutide.

A total of 16 studies were included, comprising 4 population-based studies and 12 animal and in vitro model studies. The studies examined circulating samples (serum, plasma) and tissue-level specimens including adipose tissue, myocardium, aorta, lung, kidney, hippocampus, and skeletal muscle. Common proteomics platforms were SomaScan, TMT-LC-MS/MS, DIA proteomics, phosphorylation proteomics, and mitochondrial proteomics. Multiple studies identified the PPAR signaling pathway, oxidative phosphorylation, and fatty acid metabolism, while ECM remodeling, complement/inflammatory pathways, and mTORC1 signaling were observed in some studies. The authors conclude that semaglutide is associated with proteomic changes across metabolic, cardiovascular, hepatic, pulmonary, renal, and nervous systems.

For researchers studying semaglutide, this review consolidates the fragmented proteomic evidence across human and animal models, highlighting recurring biological pathways that may underlie its pleiotropic effects. It does not establish which proteomic signatures are reproducible or clinically translatable, and it provides no quantitative synthesis or causal inference.

Key findings

The review included 16 studies: 4 population-based and 12 animal/in vitro model studies.
Proteomic changes were observed in serum, plasma, adipose tissue, myocardium, aorta, lung, kidney, hippocampus, and skeletal muscle.
PPAR signaling, oxidative phosphorylation, and fatty acid metabolism were frequently identified pathways across studies.
ECM remodeling, complement/inflammatory pathways, and mTORC1 signaling appeared in some studies.
Semaglutide-associated proteomic changes spanned metabolic, cardiovascular, hepatic, pulmonary, renal, and nervous systems.

Limitations

Small sample sizes in included studies
High subject heterogeneity
Significant differences in proteomic platforms across studies
Limited number of population-based studies

The record

Journal: Journal of endocrinological investigation
Published: 2026-07-23
PMID: 42489869 — DOI: 10.1007/s40618-026-02989-y
Funding: Natural Science Foundation of Hebei Province; Government-funded clinical medicine training excellence programme 2022
Author countries: China

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.